The long-term objective of this work is to develop and perfect methods for medicating the human dental pulp through intact dentin. This requires considerable knowledge of the regulation of both fluid and solute movement across dentin. The proposed research is designed to evaluate the rate-limiting factors controlling fluid and solute movement across dentin in vivo. The effects of acid-etching and changes in pulpal pressure on the hydraulic conductance (Lp) of dentin in vivo will be determined. The effects of cavity preparation on dentin permeability will be determined using radiosotopic methods and by Lp determination in chronic dog studies. Light and scanning electron microscopic studies will be correlated with the functional data to provide insight as to the mechanism(s) responsible for changing dentin permeability. Microliter quantities of dentinal fluid will be analyzed for total protein and compared to plasma protein concentrations to provide information about pulpal capillary protein leakage as a first step toward the use of dentinal fluid as a pulpal diagnostic procedure. Human volunteers will be used to evaluate the correlations between fluid movement across dentin and their perception of pain. This will provide a direct test of the hydrodynamic theory of dentin sensitivity. Small conical chambers will be cemented into cavities prepared in bicuspids shceduled for extraction and connected to hydrostatic pressure sources. Local anesthetic solutions will be filtered across intact dentin to see if such maneuvers can produce profound pulpal anesthesia in humans. The duration of pulpal anesthesia will be determined using lidocaine alone, and with epinephrine 1:100,000, 1:10,000 and 1:1000. The pulpal tissue pressure of sound teeth will be measured through intact dentin to permit calculation of the hydraulic conductance of human dentin in vivo. The efficacy of several agents thought to be potential dentin desensitizing agents will be tested for their ability to reduce Lp. The proposed work should provide a new drug delivery system which will be optimized so that it can be transferred from the research laboratory to the chairside.